Sequential Use of Androgen Receptor Axis-targeted Agents in Chemotherapy-naive Castration-resistant Prostate Cancer: A Multicenter Retrospective Analysis With 3-Year Follow-up

BackgroundThere has been no established clinical evidence for using sequential treatment in castration-resistant prostate cancer (CRPC). Despite evident cross-resistance, androgen receptor axis-targeted agents (ARTAs), namely abiraterone (ABI) and enzalutamide (ENZ), are often used sequentially owing to less toxicity compared with chemotherapy.Patients and MethodsA multicenter retrospective review of chemotherapy-naive patients with CRPC who had received ABI followed by ENZ (ABI-to-ENZ) or ENZ followed by ABI (ENZ-to-ABI) was conducted. Combined progression-free survival (PFS), overall survival (OS), and prostate-specific antigen (PSA) response (≥ 50% PSA decline) to each drug were compared between the 2 groups at the median follow-up of 36.0 months.ResultsThere were no significant differences in combined PFS (12.4 vs. 10.9 months; hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.72-1.23; P = .6594) or OS (28.3 vs 29.3 months; HR, 0.96; 95% CI, 0.66-1.38; P = .8314) between the ABI-to-ENZ and ENZ-to-ABI groups. PSA response rate was not significantly different in first-line ARTAs (48.9% vs. 58.4%; P = .153) but significantly higher in ENZ as a second-line ARTA (40.4% vs. 13.7%; P < .0001). Although multivariate analysis revealed that the ABI-to-ENZ sequence was associated with favorable PFS on second-line ARTA (HR, 0.65; 95% CI, 0.49-0.85; P = .0019), it was not associated with an increased combined PFS or OS.ConclusionWith relatively longer follow-up, ARTA sequence did not affect clinical outcomes of CRPC treatment except for PSA response and PFS on a second-line ARTA. These findings will be useful information in clinical decision-making, particularly in chemotherapy-unfit patients with CRPC.     

Electronic FRAIL score as a predictor of treatment outcomes in older patients with diffuse large B-cell lymphoma

IntroductionFrailty is a significant risk factor for poor outcomes among older patients with diffuse large B-cell lymphoma (DLBCL). We present an automatically derived electronic frailty screening tool (FRAIL score) as a predictor of patient outcomes.MethodsPatients aged 70 or over who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy for DLBCL between 2010 and ` were retrospectively assessed for their FRAIL scores. Measured treatment outcomes included overall survival (OS), progression-free survival (PFS), and treatment-limiting toxicity from chemotherapy.ResultsA total of 96 patients were analysed. When stratified by FRAIL score, the estimated 5-year PFS was 58%, 48% and, 0% for those with scores of 0–1, 2, and 3–5, respectively (p = 0.012). Similarly, the estimated 5-year OS for these respective groups was 60%, 60% and 0% (p = 0.010). Patients with a FRAIL score of 3–5 were also more likely than those with a score of 0–1 to need dose reduction or treatment delay due to toxicity (odds ratio [OR] 12.5, 95% confidence interval [CI] 10.42–109.72) and less likely to complete the six planned cycles of treatment (OR 0.14, 95% CI 0.03–0.77).ConclusionThe FRAIL score is independently predictive of OS, PFS, and treatment-related toxicity in older patients with DLBCL receiving R-CHOP chemotherapy. Once implemented, it provides a quick and accessible method to stratify disease and treatment-related risk among these patients.     

Diabetes and the Prognosis in Patients With Non-Hodgkin Lymphoma: A Meta-analysis of Cohort Studies

BackgroundConsensus lacks regarding the association between diabetes mellitus (DM) and the prognosis of patients with non-Hodgkin lymphoma (NHL). We aimed to systematically evaluate the above association, as well as the potential influence of metformin use in a meta-analysis of cohort studies.Materials and MethodsCohort studies investigating the association between DM and survival outcomes of patients with NHL were included by search of electronic databases that included PubMed, Embase, and Web of Science. A random-effects model was adopted to combine the results.ResultsEight cohort studies including 8652 patients with NHL were analyzed. Compared to non-DM patients with NHL, DM was associated with poor overall survival (OS, hazard ratio [HR] = 1.49, 95% confidence interval [CI]: 1.18-1.89, P < .001, I² = 69%), progression-free survival (PFS, HR = 1.30, 95% CI: 1.09-1.56, P = .004, I² = 0%), and lymphoma-specific survival (LSS, HR = 1.86, 95% CI: 1.41-2.45, P < .001, I² = 0%). Subgroup analysis showed consistent results in patients with diffuse large B-cell lymphoma (DLBCL, HR = 1.42, 1.35, and 1.95 for outcomes of OS, PFS, and LSS, respectively; P values all <.05). However, the associations between DM and these survival outcomes became nonsignificant in subgroup analysis limited to DM patients with concurrent use of metformin (HR = 1.30, 1.12, and 1.43 for outcomes of OS, PFS, and LSS, respectively; P values all > .10).ConclusionsDM is associated with poor survival outcomes in patients with B-cell NHL, which is consistent in patients with DLBCL. Concurrent metformin use in DM patients with NHL may be associated with improved survival outcomes.     

Comparison of the Effectiveness and Safety of the Oral Selective Inhibitor of Nuclear Export,Selinexor, in Diffuse Large B Cell Lymphoma Subtypes

BackgroundThe SADAL study evaluated oral selinexor in patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL) after at least 2 prior lines of systemic therapy. In this post-hoc analysis, we analyzed the outcomes of the SADAL study by DLBCL subtype to determine the effects of DLBCL subtypes on efficacy and tolerability of selinexor.Patients and MethodsData from 134 patients in SADAL were analyzed by DLBCL subtypes for overall response rate (ORR), overall survival (OS), duration of treatment response, progression-free survival, and adverse events rate.ResultsORR in the entire cohort was 29.1%, and similar in patients with germinal center (GCB) versus non-GCB DLBCL (31.7% vs. 24.2%, P = 0.45); transformed DLBCL showed a trend towards higher ORR than de novo DLBCL: 38.7% vs. 26.2% (P = 0.23). Despite similar prior treatment regimens and baseline characteristics, patients with DLBCL and normal C-MYC/BCL-2 protein expression levels had a significantly higher ORR (46.2% vs.14.8%, P = 0.012) and significantly longer OS (medians 13.7 vs. 5.1 months, hazard ratio 0.43 [95% CI, 0.23-0.77], P = 0.004) as compared with those whose DLBCL had C-MYC and BCL-2 overexpression. Among patients who had normal expression levels of either C-MYC or BCL-2 and baseline hemoglobin levels ≥ 10g/dL, ORR was 51.5% (n = 47), with median OS of 15.5 months and median PFS of 4.6 months. Similar rates of adverse events were noted in all subgroups.ConclusionsOverall, single agent oral selinexor showed strong responses in patients with limited treatment alternatives regardless of germinal center B-cell type or disease origin.     

Outcomes based on age in patients with metastatic renal cell carcinoma treated with first line targeted therapy or checkpoint immunotherapy: Older patients more prone to toxicity

ObjectivesOlder patients with metastatic renal cell carcinoma (mRCC) were underrepresented in pivotal trials.Materials and methodsConsecutive patients with mRCC treated at Aarhus University Hospital with first line tyrosine kinase inhibitors (TKI), mTOR inhibitors, or checkpoint immunotherapy (CPI) were retrospectively analyzed in age-subgroups; ≥ 75, 65–74, and < 65 years, with overall survival (OS), time-to-treatment discontinuation (TTD), and progression-free survival (PFS) as endpoints. Hazards ratios were adjusted (aHR) for International Metastatic RCC Database Consortium (IMDC) risk factors, histology, and age.ResultsOf 838 patients, 159 (19%) were ≥ 75 years, 324 (39%) 65–74 years, and 355 (42%) < 65 years. Treatments were TKI in 729 (87%) patients, mTOR in 43 (5%) and CPI in 67 (8%). Older patients ≥ 75 years compared with 65–74 years and < 65 years had lower toxicity-adjusted median doses of pazopanib, 300 mg vs. 400 mg vs. 600 mg, respectively, (p < 0.001), and sunitinib, 25 mg vs. 37.5 mg vs. 50 mg, respectively (p < 0.001); numerically fewer doses of CPI, median 2 vs. 5 vs. 5, respectively, (p = 0.2); a higher proportion had dose reduction/interruption, 76% vs. 55% vs. 41%, respectively, (p < 0.001); and shorter mean time to dose reduction/interruption, 0.5 months vs. 1.9 months vs. 3.4 months, respectively, (p < 0.001). After adjusting IMDC prognostic factors and histology in multivariate analyses, age did not impact OS (aHR 1.0; 95% CI 0.99–1.02, p = 0.2), TTD (aHR 1.0; 95% CI 0.99–1.01, p = 0.4) or PFS (aHR 1.0, 95% CI 0.99–1.01; p = 0.9).ConclusionOlder patients with mRCC were more prone to toxicity; but age did not impact outcomes. Proactive dose modification/interruption and awareness may help to reduce toxicity while maintaining efficacy.     

Timing of Autologous Stem Cell Transplantation for Multiple Myeloma in the Era of Current Therapies

BackgroundAutologous stem cell transplantation (SCT) during the initial treatment of multiple myeloma has been shown to improve progression-free survival (PFS) but not overall survival (OS). While awaiting further prospective data, we retrospectively analyzed the outcomes of patients at our program.Patients and MethodsWe included consecutive patients with newly diagnosed myeloma who had undergone stem cell harvest (SCH) from 2005 to 2014 and separated them into early (SCT within 12 months of diagnosis) and delayed (all others, including SCT not yet) groups. The outcomes were OS, PFS to first relapse, and PFS to second relapse.ResultsOf the 514 patients who had undergone SCH, 227 were in the early and 287 in the delayed groups. Patients in the delayed group who had undergone SCT had received more therapy before SCT (55% had received ≥ 2 lines vs. 6% in the early group; P < .001), had had more progressive disease at SCT (34% vs. 4%; P < .001), had received melphalan doses < 200 mg/m² (22% vs. 10%; P = .001), and had had lower rates of very good partial response or better after SCT (58% vs. 79%; P = .001). On multivariable analysis, no differences were found in median OS (90 vs. 84 months; P = .093), PFS to first relapse (40 vs. 37 months; P = .552), or PFS to second relapse (54 vs. 52 months; P = .488) between the early and delayed groups.ConclusionDelaying SCT did not affect OS or even PFS to second relapse in our cohort of patients with newly diagnosed myeloma who had received current era induction therapy.     

Characterizing Lymphoma Incidence and Disparities for a Cancer Center Catchment Region

BackgroundRacial disparities in non-Hodgkin lymphoma (NHL) are not well-elucidated for specific catchment areas, which can influence outcomes. Leveraging regional data from a population-based cancer registry may provide unique opportunities to quantify NHL disparities.Materials and MethodsUsing Surveillance, Epidemiology, and End Results (SEER) data for NHL cases diagnosed in Georgia from 2001 to 2015, we examined NHL incidence rates by lymphoma subtype and racial differences in baseline characteristics and outcomes for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Cox regression models identified predictors of overall survival (OS).ResultsSEER documented 38,504 NHL cases in Georgia from 2001 to 2015. The age-adjusted incidence rate for NHL in Georgia increased 1.03% per year, and the annual percentage change was 1.72 in blacks compared with 0.84 in whites. Compared with whites, blacks with DLBCL and FL were more likely to be diagnosed at a younger age (DLBCL, 54.1 vs. 65.5 years; P < .0001; FL, 58.4 vs. 64.0 years; P < .0001) and with B symptoms (DLBCL, 44.4% vs. 33.4%; P < .0001; FL, 28.5% vs. 21.4%; P = .004). Across racial categories, age at diagnosis > 60 years, advanced stage, and B symptoms predicted worse OS in DLBCL and FL. Blacks with DLBCL more commonly were diagnosed with stage III/IV disease (55.5% vs. 48.1%; P < .0001) and had worse 5-year relative survival (58.8% vs. 62.3%; P = .01).ConclusionsRegional cancer registry data can be used to define incidence patterns and disparities in outcomes across NHL subtypes to help define key targets for interventions in a catchment area.     

Survival outcomes of metastatic breast cancer patients by germline BRCA1/2 status in a large multicenter real-world database

The outcomes and best treatment strategies for germline BRCA1/2 mutation (gBRCAm) carriers with metastatic breast cancer (MBC) remain uncertain. We compared the overall survival and the first line progression free survival (PFS1) of patients with a gBRCAm identified at initiation of first-line treatment with those of BRCA wild-type (WT) and not-tested (NT) individuals in the ESME real-world database of MBC patients between 2008 and 2016 (NCT03275311). Among the 20 624 eligible patients, 325 had a gBRCAm, 1138 were WT and 19 161 NT. Compared with WT, gBRCAm carriers were younger, and had more aggressive diseases. At a median follow-up of 50.5 months, median OS was 30.6 (95%CI: 21.9-34.3), 35.8 (95%CI: 32.2-37.8) and 39.3 months (95% CI: 38.3-40.3) in the gBRCAm, WT and NT subgroups, respectively. Median PFS1 was 7.9 (95%CI: 6.6-9.3), 7.8 (95%CI: 7.3-8.5) and 9.7 months (95%CI, 9.5-10.0). In the multivariable analysis conducted in the whole cohort, gBRCAm status had however no independent prognostic impact on OS and PFS1. Though, in the triple-negative subgroup, gBRCAm patients had better OS and PFS1 (HR vs WT = 0.76; 95%CI: 0.60-0.97; P = .027 and 0.69; 95% CI: 0.55-0.86; P = .001, respectively). In contrast, in patients with HR+/HER2 negative cancers, PFS1 appeared significantly and OS non significantly lower for gBRCAm carriers (PFS1: HR vs WT = 1.23; 95%CI: 1.03-1.46; P = .024; OS:HR = 1.22, 95% CI: 0.97-1.52, P = .089). In conclusion, gBRCA1/2 status appears to have divergent survival effects in MBC according to IHC subtype.     

Peripheral Blood Lymphocyte-to-Monocyte Ratio at Relapse Predicts Outcome for Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma in the Rituximab Era

BackgroundPatients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have a poor prognosis, even in the rituximab era. Several studies have reported the clinical importance of the peripheral blood lymphocyte-to-monocyte ratio (LMR) in various malignancies, including lymphoma. However, the prognostic value of the LMR in relapsed/refractory DLBCL has not been well evaluated. The purpose of the present study was to investigate whether the LMR at relapse can predict clinical outcomes for relapsed/refractory DLBCL patients treated with rituximab.Patients and MethodsWe analyzed data on 74 patients with relapsed/refractory DLBCL, who were initially treated with R-CHOP (rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone) or an R–CHOP-like regimen.ResultsThere was a significant association between a low LMR (≤ 2.6) and shorter overall survival (OS; P < .001) and progression-free survival (PFS; P < .001) compared with the high LMR group (> 2.6). Multivariate analysis showed that LMR was an independent prognostic factor for OS (P < .001) and PFS (P < .001), as was the international prognostic index (IPI) at relapse for OS. In addition, the LMR had an incremental value for OS and PFS compared with the IPI at relapse.ConclusionThe LMR predicts OS and PFS outcomes in relapsed/refractory DLBCL patients treated with rituximab, and might facilitate better stratification among patients in low- and intermediate-risk IPI groups.     

Diffuse Large B Cell Lymphoma in Patients 80 Years and Older: Worse Survival After Treatment Without Increased Relapse Rates

Background: Age is an adverse prognostic factor in diffuse large B cell lymphoma (DLBCL), but there are limited data on the outcomes of patients' ≥80 years, including those treated with dose reduced chemoimmunotherapy. Patients and Methods: We conducted a retrospective analysis of 542 patients, 85 (16%) were ≥80 years of age. Results: Although the very elderly group had more frequent comorbidities and decreased performance status, 89% received therapy. Four-year PFS was 42% vs. 61% (P < .001) in patients ≥80 years vs. younger patients, while 4-year OS was 42% vs. 72% (P < .0001), respectively. In patients treated with anthracycline-containing regimens (n = 416) 4-year cumulative incidence of relapse with death as competing risk was not different between age groups. Median survival for DLBCL patients ≥80 years treated with R-CHOP or R-miniCHOP was 4.5 years. Survival after first relapse was significantly different between age groups: 5 vs. 19 months (P = .002), respectively.Conclusion: Very elderly DLBCL patients have worse OS and PFS compared with younger patients but can achieve long term disease control and potentially be cured with chemoimmunotherapy. Older DLBCL patients treated with effective regimens do not have increased rates of relapse, but outcomes after relapse remain poor.     

Comparison of Upfront Transplantation and Pretransplant Cytoreductive Therapy for Advanced Myelodysplastic Syndrome

BackgroundAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for advanced myelodysplastic syndrome (MDS). However, the value of pretransplant cytoreduction remains debatable.Patients and MethodsWe retrospectively compared the outcomes of upfront transplantation and pretransplant cytoreduction. Of 69 patients, 39 received upfront allo-HSCT and 30 received pretransplant cytoreduction, including chemotherapy (n = 16), hypomethylating agents (HMAs, n = 6), and HMAs with chemotherapy (n = 8).ResultsThe upfront group achieved similar overall survival (OS) and a trend of better progression-free survival (PFS) from diagnosis compared with the cytoreduction group (3-year PFS, 64.0% vs. 44.4%, P = .076). Posttransplant outcomes were comparable between the two groups in terms of OS, relapse-free survival (RFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM). In patients with ≥2 mutations, the upfront group achieved better OS and PFS (3-year OS, 100.0% vs. 68.6%, P = .044; 3-year PFS: 92.3% vs. 43.9%, P = .016) than the cytoreduction group. Patients achieving remission in the cytoreduction group had outcomes similar to the upfront group, but those without remission before transplantation had a significantly worse posttransplant OS (3-year OS, 46.7% vs. 75.7%, P = .038). Patients with pretransplant HMAs had better PFS than those with chemotherapy or HMAs plus chemotherapy (P < 0.05).ConclusionCompared with pretransplant cytoreduction, upfront allo-HSCT might provide more benefit to some patients with advanced MDS if there are suitable donors. HMAs would be a good alternative during the donor search.     

Prognostic Impact of ABO Blood Group on Survival in Patients With Malignant Lymphoma

BackgroundThe ABO blood group is reported to be associated with survival for several types of malignancy. We conducted a retrospective study to evaluate the prognostic significance of the ABO blood group in patients with malignant lymphoma.Patients and MethodsA total of 523 patients with malignant lymphoma were included in this study. The primary outcome measured was the association between the ABO blood group and survival.ResultsPatients with blood group B had shorter 5-year overall survival (OS) than patients with non-B blood groups (40.9% vs. 57.3%; P < .01). Among 240 patients with diffuse large B-cell lymphoma (DLBCL), patients with blood group B had shorter 5-year OS in comparison with patients with non-B blood groups (36.3% vs. 56.9%; P < .01). Among male patients with DLBCL, those with blood group B had significantly shorter 5-year OS than those with non-B blood groups (27.5% vs. 55.8%; P = .003). On the other hand, there was no significant difference in the survival between female patients with blood group B and those with non-B blood groups (5-year OS: 49.2% vs. 58.2%; P = .67). A multivariate analysis demonstrated that blood group B (hazard ratio, 1.83; 95% confidence interval, 1.21-2.78; P = .04) was an independent predictor of shorter OS in male patients with DLBCL.ConclusionThe ABO blood group is associated with survival in patients with lymphoma. Interestingly, only male patients with DLBCL with blood group B had significantly shorter OS than those male patients with DLBCL with non-B blood groups.     

BRCA1/2 Mutation Types Do Not Affect Prognosis in Ovarian Cancer Patients

Background: High grade serous ovarian carcinoma (HGSOC) is the most lethal type of epithelial ovarian cancer, with a prevalence of germline BRCA1/2 mutations as high as 20%. Our objective is to determine whether the location of mutations in the different domains of the BRCA1/2 genes affects the clinical outcome of HGSOC patients. Methods: A total of 51 women with BRCA1 or BRCA2 mutated ovarian cancer were identified. Progression-free survival (PFS) and overall survival (OS) were analyzed. Results: In our study cohort, 35 patients were carriers of germline mutations in BRCA1 and 16 in BRCA2. The median PFS time following completion of the primary therapy was 23.8 months (95% CI 20.1–27.5) and the median OS was 92.9 months (95% CI 69.8–116.1) in all BRCA carriers. After multivariate analysis, no significant association among the location or type of BRCA1/2 mutation with PFS or OS was identified. Notably, significant differences in PFS between carriers of identical mutations in the same BRCA gene were detected. Conclusions: Among HGSOC patients, BRCA1/2 carriers with mutations in different locations of the genes show no significant difference in survival outcomes, in terms of PFS and OS, suggesting the potential effect of other genetic abnormalities and co-contributing risk factors.     

Four-Year Survival With Durvalumab After Chemoradiotherapy in Stage III NSCLC—an Update From the PACIFIC Trial

IntroductionIn the Phase 3, placebo-controlled PACIFIC trial of patients with unresectable, stage III NSCLC without disease progression after concurrent chemoradiotherapy, consolidative durvalumab was associated with significant improvements in the primary end points of overall survival (OS) (hazard ratio [HR] = 0.68; 95% confidence interval [CI]: 0.53–0.87; p = 0.00251; data cutoff, March 22, 2018) and progression-free survival (PFS) (blinded independent central review; Response Evaluation Criteria in Solid Tumors version 1.1) (HR = 0.52; 95% CI: 0.42–65; p < 0.0001; February 13, 2017) with manageable safety. Here, we report updated analyses of OS and PFS, approximately 4 years after the last patient was randomized.MethodsPatients with WHO performance status of 0 or 1 (and any tumor programmed death-ligand 1 status) were randomized (2:1) to intravenous durvalumab (10 mg/kg) or placebo, administered every 2 weeks (≤12 months), stratified by age, sex, and smoking history. OS and PFS were analyzed using a stratified log-rank test in the intent-to-treat population. Medians and 4-year OS and PFS rates were estimated by the Kaplan–Meier method.ResultsOverall, 709 of 713 randomized patients received durvalumab (n/N=473/476) or placebo (n/N=236/237). As of March 20, 2020 (median follow-up = 34.2 months; range: 0.2–64.9), updated OS (HR = 0.71; 95% CI: 0.57–0.88) and PFS (HR = 0.55; 95% CI: 0.44–0.67) remained consistent with the primary analyses. The median OS for durvalumab was reached (47.5 mo; placebo, 29.1 months). Estimated 4-year OS rates were 49.6% versus 36.3% for durvalumab versus placebo, and 4-year PFS rates were 35.3% versus 19.5% respectively.ConclusionThese updated exploratory analyses demonstrate durable PFS and sustained OS benefit with durvalumab after chemoradiotherapy. An estimated 49.6% of patients randomized to durvalumab remain alive at 4 years (placebo, 36.3%), and 35.3% remain alive and progression-free (placebo, 19.5%).     

TPX2 as a Novel Prognostic Indicator and Promising Therapeutic Target in Triple-negative Breast Cancer

IntroductionTriple-negative breast cancer (TNBC), which lacks endocrine therapies and targeted therapies, has the worst prognosis of all breast cancers which remain the most common malignancy in women worldwide. Targeting protein for xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein that is strongly correlated with chromosomal instability, resulting in the development of different human tumors. Herein, we investigated the relationship between the clinical outcome of TNBC and the expression level of the TPX2 protein.Materials and MethodsPatients initially treated at Tongji Hospital for confirmed TNBC were evaluated by immunohistochemical staining and retrospectively recruited into our study. The immunohistochemical staining evaluation of TPX2 was based on the staining intensity and extent. STATA was used to analyze all the data.ResultsIn total, 97 patients with TNBC were recruited into our study. The TPX2 protein was overexpressed in almost all patients with TNBC. Our study demonstrated that an elevated TPX2 protein level was significantly associated with worse outcomes in the patients with TNBC, including worse progression-free survival (PFS) and overall survival (OS) (log-rank test, P < .001). Our model also indicated that TPX2 expression was an independent predictor of OS (hazard ratio, 2.20; 95% confidence interval, 1.13-4.28; P = .020) but not of PFS (P = .639).ConclusionIn conclusion, we demonstrated that TPX2 could be a novel prognostic marker of PFS and OS after the initial treatment of TNBC. We also revealed that TPX2 expression could serve as an independent predictor of OS but not of PFS and a promising therapeutic target in patients with TNBC.     

Increased Bone Marrow Plasma-Cell Percentage Predicts Outcomes in Newly Diagnosed Multiple Myeloma Patients

BackgroundPrevious reports have suggested that a higher bone marrow plasma-cell percentage (BMPC%) is associated with worse outcomes. However, it is unknown whether BMPC% is an independent predictor because genetic information was not available at that time. Currently the impact of BMPC% at diagnosis of multiple myeloma (MM) is not well described.Patients and MethodsWe evaluated the prognostic impact of BMPC% ≥ 60% versus < 60% in 1426 newly diagnosed MM patients. All patients had an estimation of their BMPC% at diagnosis, and the highest percentage was used. Progression-free survival (PFS) and overall survival (OS) analyses were performed by the Kaplan-Meier method. Univariate and multivariate analyses for PFS and OS using the Cox proportional hazards model were performed for age, Revised International Staging System (R-ISS) score, creatinine level, and BMPC%.ResultsBMPC% ≥ 60% was found in 562 patients (39%), and the median PFS was shorter for these patients compared to BMPC% < 60% (22.6 vs. 32.1 months; P < .0001). Also, for OS, the median was shorter for the higher BMPC% group (53.4 vs. 75.4 months; P < .0001). On the multivariate analysis for PFS, age ≥ 65 years (hazard ratio [HR], 1.46; P < .0001), R-ISS (1-2 vs. 3) (HR, 0.49; P < .0001), and BMPC% ≥ 60% (HR, 1.23; P = .015) were predictive. On the multivariate analysis for OS, age ≥ 65 years (HR, 2.23; P < .001), R-ISS (1-2 vs. 3) (HR, 0.41; P < .0001), and BMPC% ≥ 60% (HR, 1.24; P = .02) were also predictive.ConclusionBMPC% ≥ 60% at diagnosis is predictive for PFS and OS, even in a multivariate analysis that included known prognostic factors for MM.     

Prognostic value of BCL2 and TP53 genetic alterations for diffuse large B-cell lymphoma patients treated with R-CHOP

Objective:Limited data about the prognostic significance of BCL2 mutations and BCL2 copy number variations in diffuse large B-cell lymphoma (DLBCL) are available. This study aimed to comprehensively describe BCL2 genetic alterations in DLBCL patients, and examine correlation of BCL2, TP53 and other genetic alterations with outcomes in patients treated with R-CHOP.Methods:Probe capture-based high-resolution sequencing was performed on 191 patients diagnosed with de novo DLBCL. MYC, BCL2, and BCL6 protein expressions were detected by immunohistochemistry.Results:The presence of BCL2 alterations significantly correlated with poor progression-free survival (PFS) (5-year PFS: 13.7% vs. 40.8%; P = 0.003) and overall survival (OS) (5-year OS: 34.0% vs. 70.9%; P = 0.036). Importantly, patients who harbored BCL2 gain/amplifications (BCL2^GA/AMP) also had a remarkably inferior 5-year PFS (11.1% vs. 38.3%; P < 0.001) and OS (22.1% vs. 69.6%; P = 0.009). In contrast, neither BCL2 mutations nor BCL2 translocations were significantly prognostic for survival. Multivariable analyses showed that the presence of BCL2 alterations, especially BCL2^GA/AMP, TP53 mutations, and International Prognostic Index (IPI) were significantly associated with inferior PFS and OS. Novel prognostic models for OS were constructed based on 3 risk factors, including BCL2 alterations (Model 1) or BCL2^GA/AMP (Model 2), TP53 mutations, and IPI, to stratify patients into 4 risk groups with different survival outcomes.Conclusions:This study showed that DLBCL patients treated with R-CHOP, BCL2 alterations, especially BCL2^GA/AMP and TP53 mutations were significantly associated with inferior outcomes, which were independent of the IPI. The novel prognostic models we proposed predicted outcomes for DLBCL patients treated with R-CHOP, but further validation of the prognostic models is still warranted.     

Prognostic Significance of Total Lymphocyte Count,Neutrophil-to-lymphocyte Ratio,and Platelet-to-lymphocyte Ratio in Limited-stage Small-cell Lung Cancer

BackgroundWe sought reliable markers of survival and disease control among patients treated for limited-stage small-cell lung cancer (LS-SCLC).Patients and MethodsSubjects were 122 patients given (chemo)radiotherapy for LS-SCLC at MD Anderson in 2002 through 2015. Pretreatment total lymphocyte count (TLC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were analyzed for associations with overall (OS) and progression-free survival. Optimal cutoff values were identified with receiver operating characteristic curves and survival probabilities with the Kaplan-Meier method.ResultsPretreatment TLC was 1.86 × 10³/μL (±0.88); NLR, 3.44 (±3.69); and PLR, 170.53 (±101.56); corresponding cutoffs were 1.9, 2.9, and 140.1. Higher TLC was associated with superior median and 2-year OS (17.4 vs. 15.7 months and 33% vs. 29%; P = .029), and higher NLR and PLR with worse median and 2-year OS (NLR: 14.9 vs. 17.8 months, 29% vs. 31%; P = .026; PLR: 14.8 vs. 18.9 months, 24% vs. 37%; P = .009). Multivariate Cox regression adjusted for age, disease stage, number of chemotherapy cycles, and use of prophylactic cranial irradiation confirmed the links between high TLC and superior OS (hazard ratio [HR] 0.55; 95% confidence interval [CI], 0.32-0.94; P = .028) and between high NLR and PLR and inferior OS (NLR: HR, 1.86; 95% CI, 1.15-3.01; P = .011; PLR: HR, 1.72; 95% CI, 1.06-2.82; P = .030).ConclusionsBaseline lymphopenia was an indicator of poor prognosis in patients with LS-SCLC.     

Early tumour shrinkage as a prognostic factor and surrogate end-point in colorectal cancer: A systematic review and pooled-analysis

PurposeEarly tumour shrinkage (ETS), defined as a reduction of at least 20% in tumour size at first reassessment, has been recently investigated retrospectively in first-line trials of metastatic colorectal cancer (CRC), and appears to be associated with better outcomes. We have performed a systematic review and meta-analysis of published trials to evaluate the prognostic value of ETS in CRC in terms of overall survival (OS) and progression-free survival (PFS).Material and methodsAn electronic search of the PubMed, SCOPUS, EMBASE, the Web of Science, and the Cochrane Central Register of Controlled Trial databases identified trials that compared outcomes of patients with or without ETS during first-line chemotherapy for metastatic CRC. The OS, reported as a hazard ratio (HR) with a 95% confidence interval (CI), was the primary outcome measure; the correlation coefficient (R) between ETS with median OS was also estimated.ResultsTwenty-one trials from 10 publications were analysed. Overall, patients with ETS were associated with a better OS (HR, 0.58; 95% CI, 0.53 to 0.64; P < 0.00001) and PFS (HR, 0.57; 95% CI, 0.47–0.69; P < 0.00001) compared with patients who were early non-responders. However, ETS was poorly correlated with OS in terms of surrogacy (R = 0.37; 95% CI - 0.31–0.78; P = 0.28).ConclusionsETS is a good prognostic factor but an inappropriate surrogate for predicting outcome in CRC patients. These findings support ETS as prognostic tool in ascertaining earlier non-responders; however, its role as a surrogate end-point deserves further evaluation.     

Mean platelet volume predicts prognosis in patients with diffuse large B‐cell lymphoma

To determine the prognostic value of baseline mean platelet volume (MPV) in diffuse large B‐cell lymphoma (DLBCL) patients. We retrospectively analyzed 161 DLBCL patients who received R‐CHOP chemotherapy. The associations between MPV and clinicopathological factors were assessed. A low MPV (MPV ≤ 9.1 fl, cut‐off was calculated by receiver operating characteristics) was not associated with any other clinicopathological factors. * Patients with MPV ≤ 9.1 fl experienced a shorter progression‐free survival (PFS) (2‐year PFS rate, 60.6% vs 84.0%, P = 0.003) and overall survival (OS) (2‐year OS rate, 70.4% vs 87.9%, P = 0.030), compared with those with MPV > 9.1 fl. The multivariate analysis demonstrated that MPV ≤ 9.1 fl was an independent prognostic factor of OS (Hazard Ratio [HR] = 0.588, P = 0.045) and PFS (HR = 0.456, P = 0.010). Therefore, we demonstrated that low baseline MPV is an independent prognostic marker of poor outcome in patients with DLBCL.